Psychomotor stimulant-induced behavior in humans and infrahumans provides a model for psychosis and motor disorders. The biological and behavioral changes induced by acute and chronic administration of psychomotor stimulants and agonists and antagonists of neurotransmitters relevant to their actions provide a framework for investigation of basic mechanisms in psyshoses and motor disorders as well as possible development of therapeutic agents. Our goal is to provide an animal model incorporating detailed behavioral pharmacological description, as a function of age and treatment duration, of target behaviors selected to represent salient aspects of acute and chronic psychosis and motor disorders. Our prior work has shown senescent rats are hyporeactive in comparison to mature rats as measured by startle response and suggests that this may result from dominance of serotonin and/or norephinephrine mechanisms. Chronic stimulant treatment appears to decrease startle amplitude causing it to resemble that of aged Ss. Additional work has shown that chronic neuroleptic treatment potentiates hyperreactive and motor components of stereotypy equally in mature Ss while only the motor components are potentiated in older Ss. This suggests that older Ss may show supersensitivity of the nigrostriatal dopamine, but not the mesolimbic dopamine system. Systemic and microinjections into specific brain loci of psychomotor stimulants, apomorphine and agonists and antagonists of neurotransmitter systems involved in their actions will be used to elucidate the neurotransmitter bases for these differences in target behaviors as a function of age and duration of treatment. The development of kindled seizures as function of chronic psychomotor stimulant treatment and age will be investigated as a model for neuronal reorganization of limbic system mechanisms in psychosis and dementia.